Amino Acids

, Volume 41, Issue 3, pp 673–686 | Cite as

Synthesis and structural study of highly constrained hybrid cyclobutane-proline γ,γ-peptides

  • Raquel Gutiérrez-Abad
  • Daniel Carbajo
  • Pau Nolis
  • Carles Acosta-Silva
  • Juan A. Cobos
  • Ona Illa
  • Miriam Royo
  • Rosa M. Ortuño
Original Article

Abstract

Two diastereomeric series of hybrid γ,γ-peptides derived from conveniently protected derivatives of (1R,2S)- and (1S,2R)-3-amino-2,2-dimethylcyclobutane-1-carboxylic acid and cis-4-amino-l-proline joined in alternation have efficiently been prepared through convergent synthesis. High-resolution NMR experiments show that these compounds present defined conformations in solution affording very compact structures as the result of intra and inter residue hydrogen-bonded ring formation. (R,S)-cyclobutane containing peptides adopt more twisted conformations than (S,R) diastereomers. In addition, all these γ-peptides have high tendency to aggregation providing vesicles of nanometric size, which were stable when allowed to stand for several days, as verified by transmission electron microscopy.

Keywords

Hybrid γ,γ-peptides Cyclobutane cis-4-amino-l-proline Hydrogen bonds Secondary structures Self-assembly Vesicles 

Abbreviations

Boc

t-Butoxycarbonyl

tBu

t-Butyl

tBuOH

t-Butanol

CD

Circular dichroism

Cbz

Benzyl carbamate

DIPEA

N,N-Diisopropylethylamine

DMAP

4-Dimethylaminopyridine

EDAC

1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide

GABA

γ-Aminobutyric acid

HMBC

Heteronuclear multiple bond correlation

HSQC

Heteronuclear single quantum correlation

Hz

Hertz

Me

Methyl

MeOH

Methanol

NMR

Nuclear magnetic resonance

NOE

Nuclear overhauser effect

NOESY

Nuclear overhauser effect spectroscopy

ppm

Parts per million

PyBOP

Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

ROESY

Rotational nuclear overhauser effect spectroscopy

TEM

Transmission electron microscopy

TFA

Trifluoroacetic acid

THF

Tetrahydrofuran

TOCSY

Total correlation spectroscopy

Supplementary material

726_2011_912_MOESM1_ESM.docx (136.4 mb)
Supplementary material 1 (DOCX 139656 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Raquel Gutiérrez-Abad
    • 1
  • Daniel Carbajo
    • 2
  • Pau Nolis
    • 3
  • Carles Acosta-Silva
    • 1
  • Juan A. Cobos
    • 1
  • Ona Illa
    • 1
  • Miriam Royo
    • 2
  • Rosa M. Ortuño
    • 1
  1. 1.Departament de QuímicaUniversitat Autònoma de BarcelonaBarcelonaSpain
  2. 2.Combinatorial Chemistry Unit, Barcelona Science ParkUniversity of BarcelonaBarcelonaSpain
  3. 3.Servei de RMNUniversitat Autònoma de BarcelonaBarcelonaSpain

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